Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
Applicant's amendment and argument filed 08/25/2026, in response to the non-final rejection, are acknowledged and have been fully considered. Any previous rejection or objection not mentioned herein is withdrawn.
Claims 1, 3, 5, 8-10, 13, 15, 17, 20-21, 25-26, 40-46 and 48 are pending and claims 15, 17, 20-21, 25-26, 40-46 and 48 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/25/2026.
Claims 1, 3, 5, 8-10 and 13 are pending and are being examined on the merits.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefore, subject to the conditions and requirements of this title.
This rejection is maintained due to arguments filed on 08/25/2026. Claims 1, 3, 5, 8-10 and 13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The first step of the eligibility analysis evaluates whether the claim falls within a statutory category (see MPEP 2106.03). Since the claim is directed to a composition comprising “a cell-free conditioned medium from non-cancerous mammalian cells” the claim is a composition of matter. Step 2A prong one of the analyses evaluates whether the claim is a judicial exception (see MPEP 2106.04). Because the claim states the nature-based products a cell-free conditioned medium comprising a cultured substantially homogenous non-cancerous mammalian cell population; wherein at least a portion of the non-cancerous mammalian cell population is contacted by at least one small molecule cell growth signaling pathway activator before being cultured in the cell culture medium, the markedly different characteristics is performed by comparing the nature-based product limitation to its natural counterpart. In this case the application is drawn to a cell extract or the secreted components of a cell that has been stimulated by small molecules.
The claim recites the naturally occurring components found within mammalian cells. Cell extracts of mammals are made by partitioning the starting cell material into separate compositions based upon some property such as solubility in a solvent, with the soluble compounds being in one composition and the insoluble being in another composition, which compositions are then generally separated into the solvent extract of that cell versus the insoluble material composition that is generally discarded. Each composition has a different subset of the compounds originally present in the cell. In other cases, the cells can be stimulated to secrete different proteins, cytokines and small molecules as is the case for the instant application. The closest naturally occurring counterparts of extracts are the same compounds found within the extract that are found in the mammalian cells in an unseparated form, even when purified, which is chemically identical to the extracted compounds. All of these are naturally occurring in nature and are not markedly different from its naturally occurring counterpart in its natural state. The properties of the nature-based product as claimed are not markedly different than the properties of these naturally occurring counterparts found in nature as these activities would inherently be found within the cells they are secreted from. The components which would give the activities claimed in the instant invention would inherently do the same in nature as there has been nothing done in the instant invention that would make them act in any different way.
Step 2A prong two evaluates whether the claim as a whole integrates the recited judicial exception into a practical application (see MPEP 2106.04(d)). This evaluation is performed by (a) identifying whether there are any additional recited elements in the claim beyond the judicial exception and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. This judicial exception is not integrated into a practical application because the applicant only claims those extracted components broadly with a conditioned medium that is cell-free. There is no integration of the judicial exceptions into any practical application because the applicant is only claiming those judicial exceptions without reciting any specific use or incorporation into any practical application.
Doing so would be implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b).
The claims do not integrate the judicial exceptions into a practical application because in this context, such integration for a claimed product would be a physical form of the specific practical application instead of a more general composition that is not so limited.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because these components and their activity are already found naturally occurring in nature and the addition of an intended use does not impart any added benefit to the compounds or integrate the composition into a practical application.
Step 2 B evaluates whether the claim as a whole, amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (see MPEP § 2106.05(b)).
Since the naturally-occurring components as-claimed are not found together in nature, admixing the ingredients into a single formulation is considered an ‘additional element’ which must be analyzed for eligibility. Admixing naturally-occurring cellular components with a conditioned media is well-understood, routine practice in the art because mammalian cells have been grown in medium for the last century in order to keep cells alive, study various aspects of different cell types and for collecting cellular secretions to isolate and determine structures and functions of various proteins, cytokines and small molecules. Also, broadly claiming a container and label do not exclude the claimed judicial exceptions from this rejection.
Please also note, the mere modifying the concentration and proportions of the product/composition is not sufficient to remove the claimed composition from a judicial exception.
Therefore, admixing the claimed naturally-occurring ingredients at such a high degree of generality merely involves applying the natural principal and appears to be no more than a drafting effort to claim the judicial exception itself; a mixture of naturally-occurring components that is not markedly different from its’ closest-occurring natural counterpart and which does not offer significantly more than the judicial exception.
Response to Arguments
Applicant's arguments filed 08/25/2026 have been fully considered but they are not persuasive. The applicant argues that the judicial exceptions “markedly different characteristics” should be applied to the entire product and not the individual judicial exceptions. The entire product is reported to have anticancer properties, however those anticancer properties stem from the individual judicial exceptions. The applicant argues that since the product is a synthetic culture medium matrix including specific biomolecules resulting from engineered pre-culture priming that the product is not a product of nature. The fact that cells can be primed to excrete biomolecules in a lab does not make them synthetic. Even if this were the case, those synthetic components would still be subject to the judicial exceptions analyses because they are not any different than those naturally occurring and synthetic counterparts can be engineered in a lab and still be identical to what is found in nature. The human body has evolved to secrete “biomolecules” to fight cancerous cells, and the applicant is only claiming those biomolecules in a cell-free conditioned medium. The medium itself is not limited to more than judicial exceptions and the judicial exceptions being claimed are not any different than how they are found naturally existing in nature or in the human body.
The applicant argues that the conditioned media containing biomolecules is incorporated into a pharmaceutical composition which is clearly integrated into a practical application. Claiming a “pharmaceutical composition” does not structurally or functionally change the components in the composition or incorporate them into any practical application. This is such a broad limitation that it can mean many things, however none of which incorporates it into any practical application. How is it being applied? Doing so would be implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b).
Claim Rejections - 35 USC § 102 and/or-Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 3, 8-10 and 13 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Brodie Chaya and Brodie Shlomt (CN110402146A) hereinafter Chaya. This rejection is maintained with slight modifications due to arguments filed on 08/25/2026.
Regarding claims 1, 3, 8-9, Chaya teaches of extracellular matrix secreted by chorion placenta derivative mesenchymal stem cell (CH-MSC) (non-cancerous mammalian cells) groups and their conditioned mediums (see page 2, (b) iii) and teaches wherein the modified MSC groups are grown in the presence of a variety of various small molecules one of which is WNT3 agonist CAS 853220-52-7 (also referred to as BML-284) (see first para. page 22).
Furthermore Chaya recites that the pharmaceutical composition for treating disease or situation is provided according to another aspect, and described pharmaceutical composition includes Pharmaceutically acceptable adjuvant, excipient or carrier and following at least one: (c) from CH-MSC groups of conditioned mediums; With (d) extracellular matrix secreted by CH-MSC groups (see page 8). Chaya does not require the cells to be present in the medium and so it can be understood that it is the conditioned medium which is intended for treatment.
Chaya also teaches after contacting the WNT3 protein to the UC-MSCs that they were then maintained in media with horse serum or in serum-free media to facilitate further support for treatment of muscular or neurological disorders (see last para. page 21, first para., page 22). And this appears to demonstrate that the molecule is contacted to the cells and then maintained in culture medium as claimed.
Regarding claim 10, Chaya describes wherein the MSC is bone marrow derived MSC’s (see page 2, last para., page 3, last sentence, page 8 first para. etc.) and with the broadest reasonable interpretation bone marrow derived MSC’s are also bone cells.
Regarding claim 13, Chaya describes a kit (see after Summary of the invention, page 7). Chaya does not describe wherein the kit has instructions or a label however these are conventionally done in the art and would have been prima facie obvious to those having ordinary skill in the art.
Chaya does not specifically describe that the medium is cell-free however Chaya describes wherein it is the extracellular components from the modified MSCs and the conditioned medium which are useful for treating diseases. Furthermore Chaya recites that the pharmaceutical composition for treating disease or situation is provided according to another aspect, and described pharmaceutical composition includes Pharmaceutically acceptable adjuvant, excipient or carrier and following at least one: (c) from CH-MSC groups of conditioned mediums；With (d) extracellular matrix secreted by CH-MSC groups (see page 8). Chaya does not require the cells to be present in the medium and so it can be understood that it is the conditioned medium which is intended for treatment.
If Chaya does not indeed anticipate the instant claims, it would have been obvious to persons having ordinary skill in the art to not include cells in the final composition which would comprise of the MSC’s secreted components and the conditioned medium, because cells can cause unwanted immune responses due to interactions with membrane proteins.
Claim 5 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Brodie Chaya and Brodie Shlomt (CN110402146A) as applied to claims 1, 3, 8-10 above, and further in view of Dong-Young Lee et. al. (Histone H4 Is a Major Component of the Antimicrobial Action of Human Sebocytes, J Invest Dermatol. 2009 October; 129(10): 2489-2496). This rejection is maintained due to arguments filed on 08/25/2026.
Chaya teaches the instant invention however is silent on the media containing the protein H4 as claimed.
Lee teaches that histone 4 (H4) is a major component of antimicrobial action of human sebocytes. Lee teaches that cultured sebocyte fractions contained H4 which exhibited antimicrobial action (see Figure 2).
Therefore it would have been obvious to persons having ordinary skill in the art to include H4 protein in the conditioned medium taught by Chaya because as Lee teaches this protein acts as a natural antimicrobial agent when detected in cultured medium. Furthermore, including a container, label and instructions in a kit is conventional and routine in the art.
Response to Arguments
Applicant's arguments filed 08/25/2026 have been fully considered but they are not persuasive. The applicant argues that Chaya does not teach contacting the non-cancerous cells with the small molecules before being cultured. This does not appear to be the case as Chaya teaches growing in the presence of WNT3 and then maintaining the cells in culture with or without horse serum. With the broadest reasonable interpretation this would still meet the claim limitations of contacting the small molecule to the non-cancerous mammalian cell population and then culturing because maintaining a culture is the same thing as culturing and Chaya teaches that the two must be in contact.
The applicant argues that it would not be reasonable to expect the histone 4 protein taught by Lee to work as discussed in Lee’s article because the applicant argues that Lee discloses this protein is specific to terminally differentiated skin cell types (sebocytes) having specialized holocrine secretion and would not be expected to work with the CH-MSCs disclosed in Chaya. The Office did not argue that it would have been obvious to include the cells that are known for secreting the histone 4 protein, rather it would have been obvious to include the histone 4 protein itself as the protein is known for having the reported activity. Therefore, including it in medium there would be a reasonable expectation of success in it having the same function as it is known to have against microbes. For instance, Lee describes in this study, histone H4 was shown to kill P. acnes and teaches that their data suggest that histone H4 is a functionally important antimicrobial peptide released by the holocrine secretion mechanism of human sebocytes. (see para. 4-5, page 5). The fact that sebocytes secrete the protein does not alter how the protein functions as the applicant is arguing. It would be expected to have the same properties as it is a secreted protein which no longer relies on the cell it was secreted from to function.
Conclusion
Currently no claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACOB ANDREW BOECKELMAN whose telephone number is (571)272-0043. The examiner can normally be reached Monday-Friday 8am-5pm.
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JACOB A BOECKELMANExaminer, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
